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Cancer Cell. 2015 Feb 9;27(2):271-85. doi: 10.1016/j.ccell.2014.11.024. Epub 2015 Jan 29.

Deregulated Myc requires MondoA/Mlx for metabolic reprogramming and tumorigenesis.

Author information

1
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA.
2
Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Room S148, P.O. Box 358057, Seattle, WA 98109-8057, USA.
3
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
4
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Department of Ophthalmology, University of Washington, Seattle, WA 98195, USA.
5
Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Room S148, P.O. Box 358057, Seattle, WA 98109-8057, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA.
6
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
7
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, MS A2-025, P.O. Box 19024, Seattle, WA 98109-1024, USA. Electronic address: eisenman@fhcrc.org.

Abstract

Deregulated Myc transcriptionally reprograms cell metabolism to promote neoplasia. Here we show that oncogenic Myc requires the Myc superfamily member MondoA, a nutrient-sensing transcription factor, for tumorigenesis. Knockdown of MondoA, or its dimerization partner Mlx, blocks Myc-induced reprogramming of multiple metabolic pathways, resulting in apoptosis. Identification and knockdown of genes coregulated by Myc and MondoA have allowed us to define metabolic functions required by deregulated Myc and demonstrate a critical role for lipid biosynthesis in survival of Myc-driven cancer. Furthermore, overexpression of a subset of Myc and MondoA coregulated genes correlates with poor outcome of patients with diverse cancers. Coregulation of cancer metabolism by Myc and MondoA provides the potential for therapeutics aimed at inhibiting MondoA and its target genes.

PMID:
25640402
PMCID:
PMC4326605
DOI:
10.1016/j.ccell.2014.11.024
[Indexed for MEDLINE]
Free PMC Article

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